Ikarisoside A inhibits inducible nitric oxide synthase in lipopolysaccharide-stimulated RAW 264.7 cells via p38 kinase and nuclear factor-kappaB signaling pathways.
This study examined the anti-inflammatory properties of Ikarisoside A, isolated from Epimedium koreanum (Berberidaceae), in lipopolysaccharide (LPS)-stimulated macrophages. Ikarisoside A inhibited the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and mouse bone marrow-derived macrophages (BMMs) in a concentration-dependent manner. In addition, Ikarisoside A reduced the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Furthermore, Ikarisoside A inhibited the activity of p38 kinase and nuclear factor-kappaB (NF-kappaB), which are signaling molecules involved in NO production. NO production was inhibited when the cells were treated with LPS and either SB 203580 (a p38 inhibitor) or Bay 11-7082 (an inhibitory kappaB kinase 2 inhibitor). These results suggest that Ikarisoside A inhibits the production of NO by inhibiting the activity of p38 MAPK and NF-kappaB. As a result of these properties, Ikarisoside A has the potential to be used as an effective anti-inflammatory agent.
Choi
Hwa Jung
HJ
Department of Dental Pharmacology, School of Dentistry, Chonbuk National University, Jeon-Ju 561-756, Korea.
Eun
Jae-Soon
JS
Park
Young-Ran
YR
Kim
Dae Keun
DK
Li
Rihua
R
Moon
Woo Sung
WS
Park
Jeong Mi
JM
Kim
Hyung Sup
HS
Cho
Nam-Pyo
NP
Cho
Sung-Dae
SD
Soh
Yunjo
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D034181:Epimedium / Q000737:chemistry; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006027:Glycosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D006027:Glycosides; C538782:Ikarisoside A; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases